The primary aim of the proposed project is to examine transitions in the course of alcohol dependence (AD) development as they relate to risk for externalizing disorders in women. The current study integrates a developmental approach to the onset of AD with twin modeling to estimate genetic and environmental contributions to externalizing disorders and to the rate of progression to more severe drinking. The investigation extends the literature on heritable influences on AD and externalizing disorders and their common liabilities by examining AD in terms of three significant transition stages in the development of the disorder: non-use to first alcohol use, first alcohol use to onset of first alcohol-related problem (i.e., abuse or dependence symptom), and first alcohol-related problem to onset of AD. Data are drawn from a longitudinal study of alcohol use disorders and associated psychopathology in adolescent females and women. The sample consists of 3787 female twins from the Missouri Adolescent Female Twin Study. Drinking behaviors, AD symptoms, and conduct disorder (CD) symptoms were reported by participants and oppositional defiant disorder (ODD) symptoms were reported by mothers. Sources of variance in the transitions from a) non-use to first alcohol use, b) first alcohol use to onset of first alcohol problem, and c) first alcohol problem to onset of AD, will initially be modeled. These basic models will then be expanded to assess common versus unique genetic and environmental contributions to progression to a more severe drinking status across stage transitions in a trivariate model. A composite externalizing factor reflecting CD and ODD symptoms will then be partitioned into genetic and environmental components. The externalizing factor will next be integrated into the trivariate model of the three stage transitions in an effort to determine the continuity of risk across the course of AD development posed by externalizing disorders and the heritability of those cross-stage influences. The integrated model will also provide an estimate of the extent to which heritable influences on externalizing disorders are correlated with heritable influences on the alcohol use transitions. Relevance to Public Health In addition to informing etiological models of AD development, estimation of the sources of risk for progression at multiple stages in the course of AD development is critical in the establishment of developmentally appropriate prevention and intervention efforts. By identifying transition points in the course of AD in which a) environmental influences play a larger role in the rate of progression of the disorder and b) externalizing disorders are most closely linked to alcohol use behaviors, findings will direct prevention efforts to stages in the course of alcohol use when outcomes may be most easily modified. [unreadable] [unreadable] [unreadable]